title: miR-24 inhibits apoptosis and represses Bim in mouse cardiomyocytes.
abstract: Acute myocardial infarction (MI) involves necrotic and apoptotic loss of cardiomyocytes. One strategy to salvage ischemic cardiomyocytes is to modulate gene expression to promote cell survival without disturbing normal cardiac function. MicroRNAs (miRNAs) have emerged as powerful regulators of multiple cellular processes, including apoptosis, suggesting that regulation of miRNA function could serve a cardioprotective function. In this study, we report that miR-24 (miRNA-24) expression is down-regulated in the ischemic border zone of the murine left ventricle after MI. miR-24 suppresses cardiomyocyte apoptosis, in part by direct repression of the BH3-only domain-containing protein Bim, which positively regulates apoptosis. In vivo expression of miR-24 in a mouse MI model inhibited cardiomyocyte apoptosis, attenuated infarct size, and reduced cardiac dysfunction. This antiapoptotic effect on cardiomyocytes in vivo was partially mediated by Bim. Our results suggest that manipulating miRNA levels during stress-induced apoptosis may be a novel therapeutic strategy for cardiac disease.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Qian
authors.forename: Linda W
authors.initials: LW
authors.lastname: Van Laake
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Siyuan
authors.initials: S
authors.lastname: Liu
authors.forename: Michael F
authors.initials: MF
authors.lastname: Wendland
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse; D011518:Proto-Oncogene Proteins